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However, venetoclax is being increasingly used with aggressive chemotherapy regimens both in the front line and in the relapse setting. Our growing experience and intensive research demonstrate that certain genetic abnormalities are associated with venetoclax sensitivity, while others with resistance, and that resistance can emerge during treatment leading to disease relapse. In the current review, we provide a summary of the known mechanisms of venetoclax cytotoxicity, both regarding the inhibition of BCL\u20102\u2010mediated apoptosis and its effect on cell metabolism. We describe how these pathways are linked to venetoclax resistance and are associated with specific mutations. Finally, we provide the rationale for novel drug combinations in current and future clinical trials.<\/jats:p>","DOI":"10.1111\/bjh.19314","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T21:19:20Z","timestamp":1706735960000},"page":"1146-1158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Venetoclax resistance in acute myeloid leukaemia\u2014Clinical and biological insights"],"prefix":"10.1111","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7341-2167","authenticated-orcid":false,"given":"Boaz","family":"Nachmias","sequence":"first","affiliation":[{"name":"Department of Hematology, Hadassah Medical Center and Faculty of Medicine Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlomzion","family":"Aumann","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hadassah 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